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Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC pat

One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

BackgroundAcute leukemia is a bone marrow-related disease characterized by fast progression and the production of immature blood cells rather than normal ones that are classified as either acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Chemotherapy as a conventional treatment has many side effects, thus new medications that target intracellular molecules and cell surface markers on leukemic cells have been developed in the last decades.Main bodyThis review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes, includ

Papillary thyroid carcinoma in a patient with long-standing chronic lymphocytic leukemia: A case report.

The synchronous occurrence of papillary thyroid carcinoma (PTC) and chronic lymphocytic leukemia (CLL) is rare and poses diagnostic challenges, particularly in distinguishing metastatic thyroid disease from hematological lymphadenopathy. The present report documents the case of a 64-year-old female patient with long-standing CLL who presented with a malignant thyroid nodule accompanied by multiple enlarged cervical lymph nodes. A diagnosis was established through integrated immunohistochemistry, flow cytometry and multimodal imaging. After the diagnosis of synchronous PTC and CLL/SLL was confi

Изучение механизма Shengmai San для лечения аденокарциномы легких на основе биоинформатики и моделирования молекулярной динамики.

Изучение механизма Shengmai San (SMS) в лечении аденокарциномы легких (LUAD) на основе комплексной стратегии, сочетающей «сетевую фармакологию, биоинформатику, стыковку молекулярной стыковки и моделирование молекулярной динамики», в целях разработки точной стратегии комбинированной терапии и выявления потенциальных биоактивных соединений. Дифференцированные гены в LUAD были выявлены в базе данных Gene Express Omnibus с использованием R (первоначально разработанные в Bell Laboratories и в настоящее время управляемые Lucent Technologies). Из энциклопедии традиционной китайской медицины были извл

Муриновая корреляция саркомы Эпштейна-Барра и саркомы Капози (MHV-68) представляет собой ценную модель для оценки чувствительности к антивирусным препаратам и взаимодействия в комбинаторных наркотиках.

Человеческие герпесвирусы представляют собой основные человеческие патогены. Особый интерес представляют члены подсемейства < < Герпесвирина > > , поскольку они вызывают хронические заболевания, такие, как рак, изменяя клеточные процессы и вводя клетки отдыха в непрерывно расширяющуюся фазу. Кроме того, в центре внимания постоянно находятся аутоиммунные заболевания, такие, как множественный склероз. Прототипический вирус человека - герпесвирус - вирус Эпштейна - Барра (ЭБВ) оказался трудно проанализировать в целях развития противовирусной терапии из-за проблем, связанных с распрост

Exportin 1 as a Therapeutic Target to Overcome Drug Resistance in Lung Cancer.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality, with therapeutic resistance continuing to limit long-term responses. Among emerging resistance mechanisms, dysregulation of nucleocytoplasmic transport has gained attention for its ability to inactivate tumor suppressor pathways. Exportin 1 (XPO1), the primary nuclear export protein, is frequently overexpressed in NSCLC and promotes the cytoplasmic mislocalization of proteins involved in cell cycle control, apoptosis, and DNA repair. This includes key regulators such as p53, FOXO, and RB, whose inactivati

Immune System and DNA Repair Defects in Ovarian Cancer: Implications for Locoregional Approaches.

In the last few years, substantial progress has been made in the treatment of ovarian cancer, with increased knowledge about the biology of the disease. Ovarian cancer is a neoplasm strongly linked to defects in DNA repair mechanisms, where deficiency in the homologous recombination (HR) system results in a better response of ovarian cancers to therapy, whether platinum-based chemotherapy, anthracyclines, or poly (ADP-ribose) polymerase (PARP) inhibitors. More recently, it has been demonstrated that different ovarian cancer histotypes may have different immunogenicity. Interestingly, defects i

ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2.

ObjectiveMetabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes 2 (ZHX2) has been implicated in the pathogenesis of chronic liver diseases, yet its precise role and underlying mechanism in DM-induced hepatic injury remain poorly elucidated.MethodsTo investigate this, we used a high-fat diet (HFD) and streptozotocin (STZ) administration to create a DM model in mice, while high glucose (HG) exposure was used to simulate DM in vitro. Through various experiments such as lucifer

Clinical prognostic implications of EPB41L4A expression in multiple myeloma.

Background: Multiple myeloma (MM) is one of the most common incurable malignancies in malignant plasma cell disease. EPB41L4A is a target gene for the Wnt/β-catenin pathway, which is closely related to the survival of multiple myeloma cells. However, there is currently no research report on the prognostic significance of the EPB41L4A gene in MM. Methods: We studied the biological significance and prognostic significance of EPB41L4A expression in MM by integrating 1956 MM samples from 7 datasets, and explored the relationship between EPB41L4A expression and MM ISS stage, molecular type, therape

Keyword Index for Volume 93

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Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways.

Polyphenols constitute an important group of natural products that are traditionally associated with a wide range of bioactivities. These are usually found in low concentrations in natural products and are now available in nutraceuticals or dietary supplements. A group of polyphenols that include apigenin, quercetin, curcumin, resveratrol, EGCG, and kaempferol have been shown to regulate signaling pathways that are central for cancer development, progression, and metastasis. Here, we describe novel mechanistic insights on the effect of this group of polyphenols on key elements of the signaling

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics.

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and t

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

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… Conversely, the HECT-type E3 HACE1 ubiquitinates Cyclin C to promote mitochondrial fission and ROS production, thereby sensitizing cells to cisplatin-induced apoptosis; HACE1 loss or Cyclin C ubiquitination inhibition markedly reduces cisplatin sensitivity ( 118 ). …

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

Use of carfilzomib in second-line therapy and beyond for relapsed multiple myeloma.

The development of proteasome inhibitors has been a major advance in therapy of multiple myeloma, accounting, in part, for the significant increase in the survival of patients diagnosed with this disease. Bortezomib was the first proteasome inhibitor to be approved for the therapy of multiple myeloma. Carfilzomib is a second-generation proteasome inhibitor with irreversible binding to proteasome and less off-target toxicity. The drug has been approved for use in relapsed/refractory multiple myeloma. In this article, we review the use of carfilzomib as second-line therapy in multiple myeloma. W

Солитарная экстрамедуллярная плазмоцитома почки у ребёнка: описание клинического случая.

ВВЕДЕНИЕ: Солитарная экстрамедуллярная плазмоцитома (SEP) — редкое злокачественное новообразование из плазматических клеток, преимущественно встречающееся у взрослых, чаще всего в области головы и шеи. Поражение почки у детей встречается крайне редко. Представлен случай солитарной экстрамедуллярной плазмоцитомы почки у ребёнка, иллюстрирующий диагностические сложности и особенности ведения пациента. ОПИСАНИЕ КЛИНИЧЕСКОГО СЛУЧАЯ: У 10-летнего мальчика отмечалась периодическая безболевая макрогематурия. При компьютерной томографии (CT) выявлено кистозно-солидное образование размером 4,8 × 4,7 ×

Ribosomal rodeo: wrangling translational machinery in gynecologic tumors.

Gynecologic cancers are a significant cause of morbidity and mortality among women worldwide. Despite advancements in diagnosis and treatment, the molecular mechanisms underlying the development and progression of these cancers remain poorly understood. Recent studies have implicated translational machinery (ribosomal proteins (RPs) and translation factors (TFs)) as potential drivers of oncogenic processes in various cancer types, including gynecologic cancers. RPs are essential components of the ribosome, which is responsible for protein synthesis. In this review paper, we aim to explore the

Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat.

Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza()) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day with an overall response r

Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.

Gastrointestinal malignant tumors exhibit a high incidence and mortality rate among all malignancies worldwide, making them a significant concern within the field of oncology. Targeted therapy for gastrointestinal tumors has become a hot topic in recent years, and its specific mechanism remains to be further elucidated. Secreted factors, including cytokines, chemokines, and growth factors, as components of the tumor microenvironment, play a crucial role in the progression of gastrointestinal tumors. Interferon-gamma (IFN-γ) can activate these factors through JAK1/2 and STAT1 signaling (the IFN